Cervical cancer prevention and care in HIV clinics across sub‐Saharan Africa: results of a facility‐based survey

Abstract INTRODUCTION To eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub‐Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics. METHODS Our facility‐based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We performed a qualitative site‐level assessment of CC prevention and care services and analysed data from routine care of WLHIV in SSA. RESULTS Human papillomavirus (HPV) vaccination was offered in 33% of sites. Referral for CC diagnosis (42%) and treatment (70%) was common, but not free at about 50% of sites. Most sites had electronic health information systems (90%), but data to inform indicators to monitor global targets for CC elimination in WLHIV were not routinely collected in these sites. Data were collected routinely in only 36% of sites that offered HPV vaccination, 33% of sites that offered cervical screening and 20% of sites that offered pre‐cancer and CC treatment. CONCLUSIONS Though CC prevention and care services have long been available in some HIV clinics across SSA, patient and programme monitoring need to be improved. Countries should consider leveraging their existing health information systems and use monitoring tools provided by the World Health Organization to improve CC prevention programmes and access, and to track their progress towards the goal of eliminating CC.


I N T R O D U C T I O N
The World Health Organization (WHO) seeks to eliminate cervical cancer (CC) within this century, and has defined the "90-70-90" targets it expects countries to reach by 2030: 90% of girls must be vaccinated with an HPV vaccine by the time they are 15 years old; 70% of women screened with a high-performance test at 35 and 45 years; and 90% of women diagnosed with cervical pre-cancer or cancer should be treated [1].To achieve these targets, coun-tries that have a high HIV burden must adopt CC prevention strategies that meet the specific needs of girls and women living with HIV (WLHIV), since they are more susceptible to disease than HIV-negative girls and women [2,3].This requires health sector reform to deliver comprehensive prevention and care services, including expanding community awareness, biomedical and clinical interventions, improving quality assurance and monitoring mechanisms, and providing the financial and technical resources necessary to implement programmes [4,5].
When nations implement preventive HIV and CC services that meet women's needs over time and across different levels of their health systems, uptake of screening services and clinical outcomes both improve.This integrated service delivery model has been adopted by several sub-Saharan African countries that have a high HIV burden [6][7][8][9][10][11][12].But these programmes are too often opportunistic with low coverage, so gains in reducing CC incidence and mortality may wane over time.Permanent reduction in CC incidence and mortality like in high-income countries [13] must be monitored using routinely collected data that informs indicators.Without such data, countries cannot assess their progress, identify gaps and devise effective interventions against CC [1].
Previous studies reported pre-cancer treatment rates of 25.6% in WLHIV in a public hospital in South Africa, 76.2% in women regardless of HIV status in Zambia and 78% in WLHIV in one clinic in Zimbabwe [14][15][16].A 2017 systematic review suggested an extension of screening options applied to HIV-negative women, to WLHIV, with more frequent followup [2].These studies do not report on all three WHO elimination targets or on other aspects of a comprehensive CC prevention and control programme.CC prevention practices within HIV clinics are rarely described and facilities rarely report data necessary to monitor WHO targets for eliminating CC in WLHIV.
We set out to fill these gaps with a survey-based study to qualitatively assess the implementation of CC prevention services across sub-Saharan Africa (SSA) at the facility/site level and use aggregate patient data to quantitatively assess cascades for WLHIV attending HIV clinics with fairly advanced CC prevention programmes.

M E T H O D S 2.1 Study design and setting
We conducted this facility-based survey between November 2020 and July 2021 at 30 HIV clinics in four African regions that participate in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium.IeDEA is a global network that gathers and analyses routinely collected clinical data from children, adolescents and adults living with HIV across 240 HIV treatment and care sites (https://www.iedea.org/).The IeDEA regional principal investigators for central, East, southern and West Africa did a convenience sampling of 30 HIV clinics that offered CC prevention and control services on-or off-site, and had electronic or paper-based systems for data collection.

Study participants
We collected data for HPV vaccination and cervical screening in the following four populations: (a) HPV vaccination (i) Girls, adolescents/young WLHIV in care: girls aged 9-14 years and/or adolescents or young women aged 15-26 years who had at least one HIV medical care visit in the clinic during the index year (the year for which data were reported); (ii) Girls and/or adolescents and young WLHIV eligible for HPV vaccination: according to each site's eligibility criteria.
(b) Cervical screening (i) WLHIV in care: 15 years old or older, who had at least one HIV medical care visit during the index year; (ii) WLHIV eligible for cervical screening: according to each site's eligibility criteria.
We harmonized these definitions of girls and women in care to ensure data could be compared across sites in different countries.

Survey development
We constructed a survey, which we based on both the International Agency for Research on Cancer CANscreen5 tool (https://canscreen5.iarc.fr/)and the WHO Toolkit for Cervical Cancer prevention and control programmes [17].First, we organized a meeting with IeDEA principal investigators, data managers, and the CANscreen5 and WHO toolkit development team members to discuss the scope of the study, study population, site eligibility and index years for data collection.Second, the lead author (SLA-K) visited six participating sites to discuss the survey with programme teams, then revised it based on their input.The revised survey was programmed into Research Electronic Data Capture (REDCap 9.8.2), a web-based application used to create databases and projects.We offered the survey in English and French.We qualitatively assessed CC prevention and care services across six domains: (1) respondent and site characteristics; (2) HPV vaccination; (3) CC screening, diagnosis, and treatment; (4) data collection and aggregation systems; (5) evaluations and audits; and (6) decision and referral support systems.
We analysed aggregated data routinely collected for HPV vaccination, cervical screening, diagnosis and treatment services offered to WLHIV in these sites.We prioritized the WHO global indicators [17] that had been reported and included HPV vaccination proportion (a key indicator in monitoring WHO targets for eliminating CC).

Survey piloting and data collection
Between May and August 2020, we piloted the survey at two sites, one in West and one in East Africa, collected feedback and then revised the survey.Target respondents were CC prevention and control programme managers or health personnel involved in CC screening activities.We invited respondents via an email that included automatically generated links to the survey.Sites that had challenges using RED-Cap 9.8.2 printed the forms, filled them in by hand and submitted scanned copies through a secured email server.One researcher (SLA-K) manually entered scanned responses into REDCap 9.8.2 and another (MD) checked the entries.Site investigators could also check the accuracy of their site data and could query the lead author if they detected any problems.

Statistical analyses
The primary outcomes of interest for our analysis were: the availability and use of CC prevention services; and the proportion of girls vaccinated, women screened, and/or treated for cervical pre-cancer and CC.We used descriptive statistics to report site characteristics and calculated percentages for each indicator.We used a changing denominator (target approach) to calculate the CC prevention and care cascade, in which all women who reach a given step comprise the denominator for each subsequent step.The target approach highlights retention gaps where they appear in cascades [18].
We assessed the association of facility characteristics (facility location, facility type, services integration, presence of nongovernmental organization [NGO] support for CC prevention) and availability of patient-level data to inform key performance indicators using chi-square and Fischer's tests as appropriate.We reported outcomes for sites with data disaggregated by HIV status, if they included data for 10 or more eligible girls or women in care.We chose this low cut-off because many sites (especially sites that vaccinated girls) collected data on a few girls and women.Because there were few sites with sufficient data in any region, we typically reported data for the total number of sites (bolded column percentages in Tables 1-4 and Tables S1-S4).We report complete data for girls eligible for HPV vaccination, cervical screening, diagnosis, treatment and referral in Tables S6-S11.We qualitatively summarized and reported good practices observed during the site visits.All analyses were performed with Stata 16 SE (Stata Corp., College Station, TX, USA).

Sites and respondent characteristics
We included 30 sites across 14 countries in four SSA IeDEA regions: Burundi and Rwanda in central Africa; Kenya, Tanzania and Uganda in East Africa; Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in southern Africa; and Burkina Faso, Nigeria and Côte d'Ivoire in West Africa (Figure 1 and Table S12).The survey response rate was 100%.

Organizing cervical screening, demand generation and programme financing
All included sites offered cervical pre-cancer screening.These services were often integrated into the HIV clinic and provided by existing staff (47%) or in another unit where the HIV clinic was located, within the larger facility (43%) (Table 1).About a quarter of the CC screening programmes were pilot programmes (n = 2, 7%) or research studies (n = 5, 17%).Mass media campaigns (78%) and group education (74%) were commonly used to raise demand.Although 83% of sites received financial support from NGOs, less than half of sites (43%) received NGO support specifically designated for CC prevention.Clients paid the total cost (43%) or part of the cost (7%) for diagnosis of suspected cervical pre-cancer or invasive cancer and the total cost (33%) or part of the cost (20%) for pre-cancer and cancer treatment (Table 2).

Cervical pre-cancer screening and pre-cancer treatment
CC screening was provided on-site in 93% of facilities, and off-site in 7%.About an equal number of sites either screened women of any age (40%), or women between 15 and 65 years.The method commonly used to screen (83%) was visual inspection with acetic acid (VIA).HPV DNA testing (40%) and cytology (30%) were performed at less than half of the sites.The most commonly used triage test was VIA (40%).Histopathology (37%) and colposcopy (30%) were commonly used for pre-cancer diagnosis and usually conducted offsite (53%).Cryotherapy (63%), thermocoagulation (43%) and loop electrosurgical excision procedure (57%) were the most common pre-cancer treatment methods.The most common follow-up interval for screen-negative women and women treated for pre-cancer was 12 months (Table 3).

Laboratory testing and quality assurance
Laboratory testing was done either for pre-cancer only (29%) (HPV DNA testing or cytology), invasive CC diagnosis only (12%) (pathology) or both (59%) (HPV DNA testing, cytology and pathology) (Table S3).Results turnaround time varied between 1 and 4 weeks (65%) in most sites.Quality assurance coordinators who ensured that the screening programmes met quality standards were available in a little over half of the sites (59%); corresponding guidelines were available in 70% of these sites, but in 48% of all sites.Accreditation systems were available in 33% of sites that offered HPV DNA testing and 20% of sites that provided pathology services.

Referral and tracking
Referral for CC screening was most often sporadic (60%); with only 23% consistently referring women for CC screening (Table S4).Of the 25 sites that referred women for precancer treatment, 40% did so systematically and 43% did so sporadically.Of the 26 sites that referred women for CC treatment, 70% did so systematically.Thirty percent and 47% of sites had no treatment infrastructure for pre-cancer and CC, respectively.Women who had been referred were usually tracked by phone calls (48%).

Surveillance systems and data collection
The sites mainly relied on electronic data systems (90%) (Table 4); 7 of 10 sites that offered HPV vaccination collected related data, and half the sites collected some data on CC

Aggregated data: monitoring indicators reported for girls eligible for HPV vaccination and women in care at HIV clinics
Of the 30 included sites, 11 (37%) collected data for outcome assessment of girls living with HIV and WLHIV, including HPV vaccination, CC screening, pre-cancer and CC treatment; 37% (n = 11) collected some data, but did not disaggregate it by HIV status.Sites receiving financial support from NGOs were more likely to have aggregated patient data informing key performance indicators (73%) as compared to sites that did not have such support (27%) (Table S5).

HPV vaccination
Of the 10 sites that currently offered HPV vaccination, two reported HPV vaccination proportions for 10 or more girls living with HIV and eligible for HPV vaccination at their facility (Table S6); 21% of eligible girls were vaccinated in Newlands Clinic (Zimbabwe), and 88% in Kisesa (Tanzania).

Cervical pre-cancer screening
Of the 15 sites that reported collecting data on cervical screening, only 11 had disaggregated indicators by HIV status (Table 4).Cervical screening proportions ranged from 4% in Hôpital de Jour du CHU Souro Sanou (Burkina Faso) to 78% in Newlands Clinic (Zimbabwe) (Figure 2, Panel a).

Pre-cancer treatment and CC management
Pre-cancer treatment proportions were reported in 10 sites, ranging from 14% in Kanyama Hospital (Zambia) to 100% in George Health Centre (Zambia) (Figure 2, Panel b).Across all sites, there were wide disparities in attrition (proportion of women who did not reach the next necessary step of the cas-cade) between women whose screens were positive and those who were treated for pre-cancer, ranging from 0% in George Health Centre to 86% in Kanyama Hospital (Table S8).Only two sites reported data on the number of WLHIV who initiated treatment for CC; three women in Newlands Clinic (Zimbabwe), and one woman in Hôpital de Jour du CHU Souro Sanou (Burkina Faso) (Table S9).

Qualitative summary of good practices
We visited six HIV clinics and two research centres mainly in southern Africa, and recorded some good practices.These included dedicated units and staff for screening, free treatment of precancerous lesions, task shifting for screening and pre-cancer treatment, capacity enhancement for pathology, unique patient identification, data linkages and partnerships (see Supplement 13 for details).

D I S C U S S I O N
We surveyed 30 HIV clinics across 14 countries in four SSA IeDEA regions to learn how they implemented CC prevention and care and to populate indicators with routinely collected patient data.Programmes for HPV vaccination were ongoing in only a third of the sites.Less than half of sites always referred women for pre-cancer and invasive CC diagnosis and treatment, at a fee for women.Almost all sites used electronic systems to collect data, though only half routinely collected CC data, including data needed to inform WHO global monitoring indicators for CC elimination.WHO recommends HPV vaccination for primary prevention of CC and 41% of WHO member states in the African region had introduced HPV vaccination in their national immunization programmes by the end of 2019 [19].By the time we conducted our study, some sites ceased vaccinating girls and women against HPV acquisition due to the COVID-19 pandemic and because of limited financial resources dedicated to HPV vaccination.These findings align with earlier studies that identified barriers to HPV vaccination [20,21].GAVI, the Vaccine Alliance, has been trying to address financial barriers for over a decade but funding challenges persist.Although the GAVI model has helped reduce financial barriers, countries must commit to sustaining HPV vaccination programmes as they mature.
The repercussions of the COVID-19 pandemic are still not clear, but few reports attribute significant interruptions in vaccination programmes to the COVID-19 pandemic [22,23].We found little data on HPV vaccination for girls living with HIV and no previous published studies reported these esti-mates.Few studies reported data on HPV vaccination rates in the general population and data from countries in SSA are scarce [19,24].Since girls living with HIV may receive their booster vaccinations through school-based programmes, stigma could increase reluctance to get vaccinated and to report.This underserved population may benefit from innovative strategies to deliver vaccines and capture data, and all girls could benefit from programmes that increase preparedness to deliver vaccines during pandemics.
WHO recommends HPV DNA testing and triaging as a cervical screening strategy for WLHIV [3].Due to the suboptimal specificity of the HPV DNA test, triage is essential for WLHIV to distinguish between women who need immediate treatment and those who can be followed up.Although these recommendations were launched towards the end of data collection for our study, a few sites already implemented HPV DNA testing, while maintaining other visual methods for screening and triage.Insufficient infrastructure and financial constraints are obstacles to implementing screen-triage-treat strategies at many facilities, and VIA screening remains common [15,25,26].Visual screening is less resource-intensive and women are likely to be treated the same day they are diagnosed, which increases retention in care [6].Facilities that wish to transition to HPV DNA testing will have to strengthen their local laboratory infrastructure, improve their quality assurance systems and seek more financing.
Invasive CC management remains challenging in several countries in SSA mostly due to limited infrastructure, limited specialized workforce and unaffordability to women [27].A recent population-based cohort study in SSA found that only one in six women with CC received cancer-directed treatment with curative potential and about two-thirds of women never accessed treatment [28].Across sites, women were often referred for invasive CC management and mainly tracked through phone calls/messaging.Since mobile phones proliferate in SSA counties, it is feasible to text women follow-up reminders [29,30].Financial limitations are harder to overcome: earlier studies reported the cost of diagnostic tests, medication and travel as the main financial barriers [31,32].At the time of our survey, pre-cancer and CC diagnosis and treatment services were not free in about two-thirds of sites.More funding is needed to ensure women's access to invasive CC diagnosis and treatment methods in SSA to improve outcomes as for women in high-income countries [33].
Routinely collected patient data disaggregated by HIV status were rare at our study sites.Fragmented funding and data systems limit the availability of patient data, making it difficult to improve integrated health programmes [11,34].The data available did allow us to see attrition rates varied widely along the steps of CC cascades.For example, attrition rates ranged between 0% (George Health Centre, Zambia) and 86% (Kanyama, Zambia) for women screened positive who should have proceeded to pre-cancer treatment.A previous study in South Africa reported an attrition rate of about 70% between cascade steps [14], but a similar study conducted in Newlands Clinic (Zimbabwe) found attrition rates were less than 20% between cascade steps [16].Screening and attrition rates at Newlands may be lower because it receives designated funding for CC prevention and invests in human resources to monitor its programme.Keeping the longterm benefits of investing in CC prevention in mind, Governments may consider other innovative ways to sustain finance beyond grants.Quality assurance and monitoring are indispensable for any effective CC prevention programme.For monitoring to be feasible, data systems that collect data for pre-defined indicators in a consistent fashion are crucial.CC prevention facility-based indicators developed specifically for WLHIV [35] should be considered in these settings.Monitoring CC occurrence and outcomes, including incidence and survival, requires population-based cancer registries.Where electronic records exist, record linkage of cancer registries and death registries with HIV and CC screening data may help to fill gaps in HIV status and survival data, respectively [6].Although almost all sites studied had electronic data systems which have been shown to be more efficient in programme monitoring [36], only half of them collected data on CC prevention and care, and less than half linked these data to population and hospital-based cancer registries.Countries could consider implementing some of the good practices reported in Supplement 13.This could potentially improve efficiency along the screening pathway.
Our study was strengthened by the use of internationally standardized tools to co-develop our survey with country representatives, improving its validity for each context.Focusing on WLHIV allowed us to identify the needs of this underserved population and see gaps across the CC continuum that may have been overlooked in more general studies.Analysing routinely collected data gave us a clearer picture of the situation on the ground at these sites.
We were also faced with some limitations.Since we included only facilities that belong to the IeDEA consortium receiving some research funding, the situation on the ground may be worse than we describe, especially since we restricted the study to sites with more advanced CC prevention programmes.Also, the service delivery and monitoring landscape for CC may have changed since the time of data collection in some sites.

Policy implications and conclusion
Facility-based data have contributed significantly to national and global monitoring of HIV.Governments and partners have sought to provide CC prevention and care for WLHIV across SSA and data for monitoring thereof.But insufficient infrastructure and financial challenges hinder these efforts, and impede both monitoring efforts and women's access to HPV vaccination, diagnostic and treatment services as reported across the sites studied.Governments should expand access to treatment infrastructure for cervical pre-cancer, diagnostic and treatment services for invasive CC, and strengthen linkages between these primary healthcare clinics and referral services.Governments should leverage the existing electronic HIV data systems across these sites to strengthen CC data collection and monitoring.Collecting and analysing these essential data will allow these governments and stakeholders to better plan, target, tailor, and scale-up sustainable CC prevention and care interventions and track the nation's progress towards the 2030 CC elimination targets in a standardized fashion.

Figure 2 .
Figure 2. Percentage of women screened for cervical pre-cancerous lesions (Panel a) and percentage of women treated for cervical precancer (Panel b).CEPREF, Centre de Prise en charge, de Recherche et de Formation; CNTS, Centre National de Transfusion Sanguine.

) Single visit approach used b
bScreening and treatment are offered during the same visit.